Prostate cancer is the most common malignancy in men in the United States and the second leading cause of cancer mortality. Unfortunately there is no cure by standard medical treatment. Therefore, novel treatments for this devastating, common disease are desperately needed. Recent progress in the development of targeted oncolytic viral vectors offer a new strategy to combat advanced prostate cancer. The long-term goals of the research described in this proposal are to develop novel viral therapeutic agents based on recombinant vesicular stomatitis viruses (rVSVs) that can target prostate tumors in vivo. The general approach involves the production of rVSVs in which the envelope glycoprotein of VSV (VSV-G) is deleted and replaced with a targeting module that results in preferential binding of the virus to prostate tumor cells and subsequent entry into those cells. The first aim will evaluate the prostate-specific infectivity of two different rVSV vectors using several different well-characterized prostate tumor cell lines. The second aim will examine the ability of the vectors to reduce tumor burden in a transgenic, immunocompetent mouse model for prostate cancer. By design, these studies involve a significant amount of technology transfer which will occur between GTx, Inc. and The University of Tennessee Health Science Center. The immediate goals of this proposal are to obtain preliminary proof-of-principal data on rVSV targeted therapeutic vectors that will allow us to initiate discussions with the FDA in preparation for submission of an IND meeting request. The long-term goals of the research described in this proposal are to develop novel viral therapeutic agents based on recombinant vesicular stomatitis viruses (rVSVs) that can target prostate tumors in patients.